Induction by lysophosphatidic acid of peritoneal and pleural metastases of intestinal cancers induced by azoxymethane in Wistar rats

The effects of 1-oleoyl lysophosphatidic acid on the induction of metastasis from intestinal adenocarcinomas induced in rats by azoxymethane and on RhoA activity in the tumors were investigated in male Wistar rats. Rats were given a weekly s.c. injection of azoxymethane (7.4 mg/kg body weight) for 10 weeks and, from week 16, s.c. injection of lysophosphatidic acid (5 or 15 microg/kg body weight) every other day until the end of the experiment in week 45. Lysophosphatidic acid at both dosages significantly increased the incidence of peritoneal metastasis. Its administration at higher dosage also significantly enhanced the development of pleural metastasis. Although lysophosphatidic acid at both dosages had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors, its administration at both dosages significantly increased the incidence of vessel invasion of adenocarcinomas. Lysophosphatidic acid also increased the activity of RhoA in the tumors, but not the cellular proliferation and vascularity of the colon tumors. Our findings indicate that lysophosphatidic acid significantly increased the incidence of peritoneal and/or pleural metastases from intestinal adenocarcinomas induced in rats by azoxymethane through RhoA activation.